Drugs Affecting the Drugs Affecting the Cardiovascular SystemCardiovascular System

Felix Hernandez, M.D.Felix Hernandez, M.D.

DiureticsDiuretics Thiazide DiureticsThiazide Diuretics

ChlorothiazideChlorothiazide MOA: inhibits sodium and chloride reabsorption MOA: inhibits sodium and chloride reabsorption

in the distal tubulein the distal tubule Indication: is the ideal starting agent for HTN. Indication: is the ideal starting agent for HTN.

Is also used to treat chronic edema and Is also used to treat chronic edema and hypercalcuriahypercalcuria

Side Effects: hypokalemia, hyponatremia, Side Effects: hypokalemia, hyponatremia, hyperglycemia, hyperglycemia,

Contraindications: pregnancy, anuriaContraindications: pregnancy, anuria

DiureticsDiuretics Loop DiureticsLoop Diuretics

Furosemide (Lasix)Furosemide (Lasix) MOA: inhibits chloride reabsorption in the thick MOA: inhibits chloride reabsorption in the thick

ascending loop. Causes high losses of potassium ascending loop. Causes high losses of potassium in the urine.in the urine.

Indications: preferred diuretic for patients with a Indications: preferred diuretic for patients with a low GFR and in hypertensive emergencies. Is low GFR and in hypertensive emergencies. Is also used for edema and to lower serum also used for edema and to lower serum potassium levelspotassium levels

Side Effects: hyponatremia, hypokalemia, Side Effects: hyponatremia, hypokalemia, hypocalcemia, dehydration, hypotension, hypocalcemia, dehydration, hypotension, ototoxicityototoxicity

Contraindications: anuria and electrolyte Contraindications: anuria and electrolyte depletiondepletion

DiureticsDiuretics Potassium Sparing DiureticsPotassium Sparing Diuretics

AmilorideAmiloride MOA: directly increases sodium excretion and decreases MOA: directly increases sodium excretion and decreases

potassium secretion in the DCTpotassium secretion in the DCT Indications: used in conjunction with other diuretics to Indications: used in conjunction with other diuretics to

treat HTNtreat HTN Side Effects: Hyperkalemia, glucose intolerance in DM Side Effects: Hyperkalemia, glucose intolerance in DM

patientspatients Has a more rapid onset than SpironolactoneHas a more rapid onset than Spironolactone

Spironolactone (Aldactone)Spironolactone (Aldactone) MOA: Antagonist of AldosteroneMOA: Antagonist of Aldosterone Indications: Used with thiazides for edema related to Indications: Used with thiazides for edema related to

CHF, cirrhosis and nephrotic syndrome. Also used to CHF, cirrhosis and nephrotic syndrome. Also used to diagnose and treat hyperaldosteronismdiagnose and treat hyperaldosteronism

Side Effects: Same as Amiloride plus endocrine Side Effects: Same as Amiloride plus endocrine imbalances (hirsutism, oily skin, acne)imbalances (hirsutism, oily skin, acne)

DiureticsDiuretics Osmotic DiureticsOsmotic Diuretics

MannitolMannitol MOA: osmotically inhibits sodium and water MOA: osmotically inhibits sodium and water

reabsorptionreabsorption Indications: ARF, brain edema, removing OD of Indications: ARF, brain edema, removing OD of

some drugssome drugs Side Effects: headache, dizziness, polydipsia, Side Effects: headache, dizziness, polydipsia,

confusion, chest painconfusion, chest pain

Presynaptic Adrenergic Presynaptic Adrenergic BlockersBlockers

Clonidine Clonidine alpha 2 alpha 2 Methyldopa Methyldopa methylnorepinephrine methylnorepinephrine

Peripheral Anti-adrenergicsPeripheral Anti-adrenergics ReserpineReserpine

MOA: partially depletes catecholamine MOA: partially depletes catecholamine stores in the PNS and CNS causing a stores in the PNS and CNS causing a decrease in TPR, HR and COdecrease in TPR, HR and CO

Indications: seldom used for mild to Indications: seldom used for mild to moderate HTNmoderate HTN

Side Effects: parasympathetic Side Effects: parasympathetic predominancepredominance

Contraindications: CHF, asthma, Contraindications: CHF, asthma, bronchitis, PUD, depression. All related to bronchitis, PUD, depression. All related to the parasympathetic predominancethe parasympathetic predominance

Alpha and Beta BlockersAlpha and Beta Blockers Alpha-1 BlockersAlpha-1 Blockers

PrazosinPrazosin Doxazosin (Cardura)Doxazosin (Cardura)

Mixed alpha and beta blockersMixed alpha and beta blockers LabetololLabetolol Carvedilol (Coreg)Carvedilol (Coreg)

Can cause further suppression of a failing heartCan cause further suppression of a failing heart

Beta BlockersBeta Blockers AtenololAtenolol

Preferentially blocks Beta-1 receptorsPreferentially blocks Beta-1 receptors Metoprolol (Lopressor)Metoprolol (Lopressor) TimololTimolol

VasodilatorsVasodilators ACE InhibitorsACE Inhibitors

MOA: Inhibit angiotensin converting enzyme in MOA: Inhibit angiotensin converting enzyme in the lung which reduces the production of the lung which reduces the production of angiotensin II a vasoconstrictor. Also suppresses angiotensin II a vasoconstrictor. Also suppresses aldosterone.aldosterone.

Indications: HTN, DOC for HTN with DM, CHF, MI Indications: HTN, DOC for HTN with DM, CHF, MI for reperfusionfor reperfusion

Side Effects: first dose hypotension, dizziness, dry Side Effects: first dose hypotension, dizziness, dry hacking coughhacking cough

Contraindications: pregnancy, bilateral renal Contraindications: pregnancy, bilateral renal artery stenosisartery stenosis

Drugs:Drugs: CaptoprilCaptopril LisinoprilLisinopril EnalaprilEnalapril

VasodilatorsVasodilators Angiotensin Receptor Blockers (ARB)Angiotensin Receptor Blockers (ARB)

MOA: antagonist at angiotensin II receptorMOA: antagonist at angiotensin II receptor Indications: HTNIndications: HTN Side Effects: hypotension and dizzinessSide Effects: hypotension and dizziness Contraindications: pregnancyContraindications: pregnancy Drugs:Drugs:

Losartan (Cozaar)Losartan (Cozaar) Valsartan (Diovan)Valsartan (Diovan)

Direct VasodilatorsDirect Vasodilators HydralazineHydralazine

MOA: relaxes arterioles (not veins) MOA: relaxes arterioles (not veins) independent of sympathetic interactions. independent of sympathetic interactions.

Causes a decrease in BP with a reflex Causes a decrease in BP with a reflex tachycardia, increased CO and increased renal tachycardia, increased CO and increased renal blood flowblood flow

Indications: moderate HTN, can be used in Indications: moderate HTN, can be used in pregnant women with HTNpregnant women with HTN

Side Effects: reflex tachycardia, fluid Side Effects: reflex tachycardia, fluid retention, Lupus like syndrome, peripheral retention, Lupus like syndrome, peripheral neuritis with long term treatment due to vit. neuritis with long term treatment due to vit. B6B6

Contraindications: patients with ischemic Contraindications: patients with ischemic heart diseaseheart disease

Direct VasodilatorsDirect Vasodilators NitroprussideNitroprusside

MOA: is converted to nitric oxide which MOA: is converted to nitric oxide which induces cGMP which then relaxes smooth induces cGMP which then relaxes smooth muscles by dephosphorylating myosinmuscles by dephosphorylating myosin

Indications: Hypertensive crisisIndications: Hypertensive crisis Side Effects: severe hypotension, cyanide Side Effects: severe hypotension, cyanide

toxicity and hepatotoxicitytoxicity and hepatotoxicity Contraindications: noneContraindications: none

Calcium Chanel BlockersCalcium Chanel Blockers Verapamil (Isopten)Verapamil (Isopten)

MOA: blocks calcium influx causing MOA: blocks calcium influx causing dilation of peripheral arterioles and dilation of peripheral arterioles and reducing afterload.reducing afterload.

Indications: DOC for acute paroxysmal Indications: DOC for acute paroxysmal supraventricular tachycardia, DOC to slow supraventricular tachycardia, DOC to slow ventricular response in A-fibventricular response in A-fib

Side Effects: constipation, hypotension, Side Effects: constipation, hypotension, bradycardia, edema, dizzinessbradycardia, edema, dizziness

Contraindications: patients on IV Beta Contraindications: patients on IV Beta blockers or Digitalis, A-V node blocks, blockers or Digitalis, A-V node blocks, heart failure, hypotensionheart failure, hypotension

Calcium Chanel BlockersCalcium Chanel Blockers Diltiazem (Cardizem)Diltiazem (Cardizem)

MOA: dilates peripheral arterioles leading MOA: dilates peripheral arterioles leading to a decreased afterload, increases to a decreased afterload, increases oxygen supply to the myocardium by oxygen supply to the myocardium by preventing sympathetic-induced coronary preventing sympathetic-induced coronary artery spasm.artery spasm.

Indications: reduction of angina episodes, Indications: reduction of angina episodes, increased exercise tolerance in stable increased exercise tolerance in stable angina, HTNangina, HTN

Side Effects: edema, headache, rashSide Effects: edema, headache, rash Contraindications: AV node block, SSS, Contraindications: AV node block, SSS,

hypotension, pulmonary congestionhypotension, pulmonary congestion

Calcium Chanel BlockersCalcium Chanel Blockers Nifedipine (Procardia)Nifedipine (Procardia)

MOA: more potent peripheral vasodilation, MOA: more potent peripheral vasodilation, doesn’t dilate coronary arteries, causes a doesn’t dilate coronary arteries, causes a reflex in crease in HR and COreflex in crease in HR and CO

Indications: no longer used as a single Indications: no longer used as a single agent due to toxicityagent due to toxicity

Side Effects: MI, peripheral edema, Side Effects: MI, peripheral edema, pulmonary edema, transient hypotension, pulmonary edema, transient hypotension, reflex tachycardiareflex tachycardia

Contraindications: hypotensionContraindications: hypotension

Anti-anginal AgentsAnti-anginal Agents NitratesNitrates

NitroglycerinNitroglycerin MOA: dilates large myocardial arteries to increase MOA: dilates large myocardial arteries to increase

blood flow to the heart. Reduces cardiac preload blood flow to the heart. Reduces cardiac preload by reducing venous tone which allows pooling of by reducing venous tone which allows pooling of blood in the peripheryblood in the periphery

Indications: DOC for angina. Used immediately Indications: DOC for angina. Used immediately before exercise or stress to prevent ischemic before exercise or stress to prevent ischemic episodesepisodes

Side Effects: hypotension with rebound Side Effects: hypotension with rebound tachycardia, cerebral ischemia, contact dermatitis tachycardia, cerebral ischemia, contact dermatitis with transdermal, aggravation of peripheral edemawith transdermal, aggravation of peripheral edema

Isosorbide DinitrateIsosorbide Dinitrate Used for prophylaxis of angina not for acute Used for prophylaxis of angina not for acute

attacksattacks Has a faster onset of action sublingual than oralHas a faster onset of action sublingual than oral

Cardiac GlycosidesCardiac Glycosides DigoxinDigoxin

MOA: inhibits sodium/potassium ATPase and MOA: inhibits sodium/potassium ATPase and increases the inward current of calcium. This leads increases the inward current of calcium. This leads to an increased contraction, increased CO and to an increased contraction, increased CO and decreased heart size, venous return and blood decreased heart size, venous return and blood volume. volume.

Causes diuresis by increased renal perfusion. Causes diuresis by increased renal perfusion. Slows ventricular rate in A-fib by increased sensitivity of AV Slows ventricular rate in A-fib by increased sensitivity of AV

nodes to vagal inhibition. nodes to vagal inhibition. Increases peripheral resistanceIncreases peripheral resistance

Indications: heart failure, A-fib, paroxysmal Indications: heart failure, A-fib, paroxysmal tachycardiatachycardia

Side Effects: bradycardia, nodal blocks, arrhythmiasSide Effects: bradycardia, nodal blocks, arrhythmias Contraindications: V-fib, severe bradyacrdia, allergic Contraindications: V-fib, severe bradyacrdia, allergic

reactions to drug classreactions to drug class

Drugs for Lipid DisordersDrugs for Lipid Disorders CholestyramineCholestyramine

MOA: forms insoluble complexes with bile MOA: forms insoluble complexes with bile salts allowing them to be excreted in salts allowing them to be excreted in feces. The body compensates by feces. The body compensates by increasing the number of LDL receptors increasing the number of LDL receptors and oxidizing cholesterol to bile acidsand oxidizing cholesterol to bile acids

Indications: LDL>190 or 160 with 2 risk Indications: LDL>190 or 160 with 2 risk factorsfactors

Lipid Profile Effects: Lipid Profile Effects: decreases TC, and LDLdecreases TC, and LDL Increases Triglycerides, VLDL and HDLIncreases Triglycerides, VLDL and HDL

Drugs for Lipid DisordersDrugs for Lipid Disorders NiacinNiacin

MOA: unclear, may reduce VLDL synthesis MOA: unclear, may reduce VLDL synthesis and secretionand secretion

Indications: same as CholestyramineIndications: same as Cholestyramine Profile changes:Profile changes:

Decreases TC, triglycerides, VLDL, and LDLDecreases TC, triglycerides, VLDL, and LDL Increases HDLIncreases HDL

Drugs for Lipid DisordersDrugs for Lipid Disorders Ezetimibe (Zetia)Ezetimibe (Zetia)

MOA: inhibits cholesterol absorption in the MOA: inhibits cholesterol absorption in the GIGI

Indications: hypercholesterolemiaIndications: hypercholesterolemia Profile Changes:Profile Changes:

Decreases LDL and triglyceridesDecreases LDL and triglycerides Increases HDLIncreases HDL

StatinsStatins MOA: inhibit HMG-CoA reductase in the liver MOA: inhibit HMG-CoA reductase in the liver

which is the enzyme that catalyzes the rate which is the enzyme that catalyzes the rate limiting step in cholesterol synthesis.limiting step in cholesterol synthesis.

Indications: SameIndications: Same Profile Changes:Profile Changes:

Decreases TC, LDL, VLDL and TriglyceridesDecreases TC, LDL, VLDL and Triglycerides Increases HDLIncreases HDL

Side Effects: MyalgiaSide Effects: Myalgia Drugs:Drugs:

Simvastatin (Zocor)Simvastatin (Zocor) Atorvastatin (Lipitor)Atorvastatin (Lipitor) Rosuvastatin (Crestor)Rosuvastatin (Crestor)

AnticoagulantsAnticoagulants HeparinHeparin

MOA: binds to antithrombin III forming a MOA: binds to antithrombin III forming a complex which then binds to and inhibits complex which then binds to and inhibits activated clotting factors.activated clotting factors.

Indications: DVT and PE prophylaxis post-Indications: DVT and PE prophylaxis post-op, maintaining extracorporeal circulation op, maintaining extracorporeal circulation with open heart surgery and dialysis, and with open heart surgery and dialysis, and achieving immediate anticoagulationachieving immediate anticoagulation

Side Effects: bleeding, hemorrhage, Side Effects: bleeding, hemorrhage, thrombocytopenia, necrosis at injection thrombocytopenia, necrosis at injection sitesite

Notes: Protamine Sulfate inactivates it and Notes: Protamine Sulfate inactivates it and can be used as an antagonist if severe can be used as an antagonist if severe bleeding occurs. Monitor PTTbleeding occurs. Monitor PTT

AnticoagulantsAnticoagulants WarfarinWarfarin

MOA: antagonizes vitamin K and inhibits MOA: antagonizes vitamin K and inhibits the synthesis of vitamin K dependent the synthesis of vitamin K dependent clotting factors (II, VII, IX, and X)clotting factors (II, VII, IX, and X)

Indications: DVT, IHD, PE, artificial heart Indications: DVT, IHD, PE, artificial heart valves, A-fibvalves, A-fib

Side Effects: bleeding, hemorrhage, Side Effects: bleeding, hemorrhage, necrosisnecrosis

Notes: Monitor PTNotes: Monitor PT

Antiplatelet AgentsAntiplatelet Agents Aspirin/IbuprofenAspirin/Ibuprofen

MOA: inhibits cyclooxygenase thus blocking MOA: inhibits cyclooxygenase thus blocking platelet aggregationplatelet aggregation

Indications: to reduce the risk of recurrent TIA or Indications: to reduce the risk of recurrent TIA or stroke, reduce risk of MI in patients with unstable stroke, reduce risk of MI in patients with unstable angina or prior infarctionangina or prior infarction

Side Effects: GI ulceration, bleeding hemorrhageSide Effects: GI ulceration, bleeding hemorrhage Clopidogrel (Plavix)Clopidogrel (Plavix)

MOA: blocks platelet aggregation by inhibiting MOA: blocks platelet aggregation by inhibiting ADP receptorADP receptor

Indications: reduction of atherosclerotic eventsIndications: reduction of atherosclerotic events Side Effects: neutropenia and same as aspirinSide Effects: neutropenia and same as aspirin

Thrombolytic AgentsThrombolytic Agents StreptokinaseStreptokinase

MOA: activates plasminogen to plasmin. MOA: activates plasminogen to plasmin. Plasmin digests fribrin and fibrinogen into Plasmin digests fribrin and fibrinogen into degradation products which also cause degradation products which also cause anticoagulation by inhibiting the formation anticoagulation by inhibiting the formation of fibrin.of fibrin.

Indications: to lyse thrombi in ischemic Indications: to lyse thrombi in ischemic coronary arteries after infarction. PE, DVT, coronary arteries after infarction. PE, DVT, occluded cannulaoccluded cannula

Side Effects: bleeding, bruising, rare but Side Effects: bleeding, bruising, rare but can have an anaphylactic response (strep can have an anaphylactic response (strep toxin)toxin)

Thrombolytic AgentsThrombolytic Agents Tissue Plasminogen Activator (TPA)Tissue Plasminogen Activator (TPA)

MOA: binds to fibrin, then activates fibrin-MOA: binds to fibrin, then activates fibrin-bound plasminogen to plasminbound plasminogen to plasmin

Indications: to reperfuse coronary arteries Indications: to reperfuse coronary arteries that are occludedthat are occluded

Side Effects: hematoma at catheterization Side Effects: hematoma at catheterization sitesite

Alteplase/ReteplaseAlteplase/Reteplase MOA: recombinant form of TPAMOA: recombinant form of TPA Indications: Acute MI, Ischemic stroke, PEIndications: Acute MI, Ischemic stroke, PE Side Effects: BleedingSide Effects: Bleeding